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BackgroundLactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain.ObjectiveTo evaluate lactation and the 2-year incidence of DM after GDM pregnancy.DesignProspective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030).SettingIntegrated health care system.Participants1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011.MeasurementsThree in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders.ResultsOf 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios.LimitationRandomized design is not feasible or desirable for clinical studies of lactation.ConclusionHigher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery.Primary funding sourceNational Institute of Child Health and Human Development.

ObjectivesLactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance.MethodsThe Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6-9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models.ResultsIncreasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%-28% lower fasting triglycerides, 15%-21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04).ConclusionHigher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.

OBJECTIVES: Bone mineral density (BMD) and fracture risk calculators (eg, the Fracture Risk Assessment Tool [FRAX]) guide primary prevention care in postmenopausal women. BMD scores use non-Hispanic White (NHW) reference data for T-score classification, whereas FRAX incorporates BMD, clinical risk factors, and population differences when calculating risk. This study compares findings among Asian, Black, and NHW women who underwent osteoporosis screening in a US health care system. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Asian, Black, and NHW women aged 65 to 75 years who underwent BMD testing (with no recent fracture, osteoporosis therapy, metastatic cancer, multiple myeloma, metabolic bone disorders, or kidney replacement therapy) were compared across the following measures: femoral neck BMD (FN-BMD) T-score (normal --1, osteoporosis --2.5), high FRAX 10-year hip fracture risk (FRAX-Hip 3%), FRAX risk factors, and diabetes status. RESULTS: Among 3640 Asian women, 23.8% had osteoporosis and 8.7% had FRAX-Hip scores of at least 3% (34.5% among those with osteoporosis). Among 11,711 NHW women, 12.3% had osteoporosis and 17.2% had FRAX-Hip scores of at least 3% (84.8% among those with osteoporosis). Among 1711 Black women, 68.1% had normal FN-BMD, 4.1% had BMD-defined osteoporosis, and 1.8% had FRAX-Hip scores of at least 3% (32.4% among those with osteoporosis). Fracture risk factors differed by group. Diabetes was 2-fold more prevalent in Black and Asian (35% and 36%, respectively) vs NHW (16%) women. CONCLUSIONS: A large subset of Asian women have discordant BMD and FRAX scores, presenting challenges in osteoporosis management. Furthermore, FN-BMD and especially FRAX scores identified few Black women at high fracture risk warranting treatment. Studies should examine whether fracture risk assessment can be optimized in understudied racial minority populations, particularly when findings are discordant. [ABSTRACT FROM AUTHOR]

Objective: There is increasing recognition that cardiovascular disease (CVD) risk factors vary by Asian subgroups. We examined CVD risk factor prevalence among Vietnamese adults in a northern California health plan. Methods: We used electronic health record data to examine smoking, overweight/obesity (body mass index ≥23.0 kg/m2), obesity (body mass index ≥27.5 kg/m2), prediabetes, diabetes, and hypertension among middle-aged (n = 12 757; aged 45-64 years) and older (n = 3418; aged 65-84 years) Vietnamese adults, including 37.8% whose preferred language was Vietnamese. Findings were compared with East Asian adults. Results: Current smoking prevalence was 20.3% for middle-aged men, 7.0% for older men, and <1% for women in both age groups. Obesity prevalence was 12.0% for older men, 17.9% for middle-aged men, and 10% for women in both age groups. Among middle-aged men and women, 20.9% and 17.0% had hypertension and 13.5% and 8.5% had diabetes, respectively. Among older men and women, 64.0% and 60.0% had hypertension and 32.8% and 29.3% had diabetes, respectively. In both age groups, Vietnamese language preference was associated with higher risk of smoking (men only) and of diabetes and hypertension (women only). Compared with East Asian adults, Vietnamese adults had lower obesity prevalence but similar prevalence of diabetes, prediabetes, and hypertension. Vietnamese men were more likely and Vietnamese women less likely than East Asian adults to be current smokers. Conclusions: Study results suggest that more research on health conditions, lifestyle, and social factors among Vietnamese American adults is needed to develop culturally competent interventions to reduce CVD risk in this growing ethnic group. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6-9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS--We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS--Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (≤6 oz formula per 24 h) groups, respectively, had lower adjusted mean (95% CI) group differences in fasting plasma glucose (mg/dL) of -4.3 (-7.4 to -1.3) and -5.0 (-8.5 to -1.4), in fasting insulin (µU/mL) of -6.3 (-10.1 to -2.4) and -7.5 (-11.9 to -3.0), and in 2-h insulin of -21.4 (-41.0 to -1.7) and -36.5 (-59.3 to -13.7) (all P < 0.05). Exclusive or mostly breastfeeding groups had lower prevalence of diabetes or prediabetes (P = 0.02). CONCLUSIONS--Higher intensity of lactation was associated with improved fasting glucose and lower insulin levels at 6-9 weeks' postpartum. Lactation may have favorable effects on glucose metabolism and insulin sensitivity that may reduce diabetes risk after GDM pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess whether the risk of incident diabetes was increased with the use of second-generation antipsychotics (SGAs) in a large diverse cohort of children. METHODS: A retrospective study was conducted by using the administrative databases of 3 health plans participating in the Health Maintenance Organization Research Network. Children 5 to 18 years of age who initiated SGA therapy between January 2001 and December 2008 and 2 comparison groups, namely, nonusers of psychotropic drugs and users of antidepressant medications, were identified. Diagnoses from inpatient and outpatient records, pharmacy dispensings, and outpatient laboratory results were used to identify incident cases of diabetes. RESULTS: The crude incidence rate of diabetes for the SGA-exposed cohort was 3.23 cases per 1000 person-years (95% confidence interval [CI]: 1.67-5.65), compared with 0.76 cases per 1000 person-years (95% CI: 0.49-1.12) among nonusers of psychotropic medications and 1.86 cases per 1000 person-years (95% CI: 1.12-2.90) among antidepressant users. The risk of incident diabetes was significantly increased among SGA users (unadjusted incidence rate ratio: 4.24 [95% CI: 1.95- 8.72]) in comparison with nonusers of psychotropic medications but was not significantly increased in comparison with antidepressant medication users (unadjusted incidence rate ratio: 1.74 [95% CI: 0.77-3.78]). CONCLUSIONS: Although we found a potentially fourfold increased rate of diabetes among children exposed to SGAs, the findings were inconsistent and depended on the comparison group and the outcome definition. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated associations of insulin sensitivity, metabolic syndrome, and diabetes mellitus with single nucleotide polymorphism (SNP) variants from sex hormone biosynthesis and action in women of 4 races/ethnicities. DNA was extracted from transformed cell samples of 1,538 women in the Study of Women’s Health Across the Nation (SWAN). African American, Caucasian, Chinese, and Japanese women in SWAN enrolled in the Sex Steroid Hormone Genetics Protocol from whom fasting glucose and insulin measures (for estimating insulin sensitivity), diabetes status, and metabolic syndrome classification were obtained. SNPs from the genes encoding aromatase (CYP 19), 17β-hydroxysteroid dehydrogenase (17HSD) type 1, and the estrogen receptors–α (ESR1) and –β (ESR2) were measured. The prevalence of metabolic syndrome was 20% in Chinese women, 22% in Japanese women, 28% in Caucasian women, and 43% in African American women. The prevalence of diabetes was 3% in Chinese women, 4% in Japanese women, 7% in Caucasian women, and 19% in African American women. Significant associations of CYP 19 genotypes and insulin sensitivity were observed in African American, Caucasian, and Japanese women. Selected ESR1 and ESR2 genotypes were associated with insulin sensitivity and metabolic syndrome only in Japanese and Chinese women. The strongest associations related 17HSD genotypes to diabetes in Caucasian women, with odds ratios ranging from 4.4 to 7.5 and confidence intervals that excluded the null value. We observed strong associations between variations in sex hormone biosynthesis and function genes with insulin sensitivity, the metabolic syndrome, and diabetes that varied by race/ethnicity. The strong association of 17HSD and diabetes in Caucasian women has not been previously reported and should be further investigated. [Copyright &y& Elsevier]

Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D. The Kaiser Permanente E valuating N utritional Inte r ventions in Food- I nse c ure H igh-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy. The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D. [ABSTRACT FROM AUTHOR]

Background: The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood.Objectives: The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care.Methods: The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus.Results: Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64).Conclusions: In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups. [ABSTRACT FROM AUTHOR]

Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug. [ABSTRACT FROM AUTHOR]